Humoral correlates of protection againstMycobacterium tuberculosisfollowing intravenous Bacille Calmette-Guérin vaccination in rhesus macaques Article Swipe
Edward B. Irvine
,
Patricia A. Darrah
,
Shu Wang
,
Chuangqi Wang
,
Ryan P. McNamara
,
Mario Roederer
,
Robert A. Seder
,
Douglas A. Lauffenburger
,
JoAnne L. Flynn
,
Sarah M. Fortune
,
Galit Alter
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.07.31.551245
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.07.31.551245
Altering the route of Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal vaccination to high-dose intravenous (IV) vaccination resulted in a high level of protection against Mycobacterium tuberculosis ( Mtb ) infection, providing an opportunity to uncover immune correlates and mechanisms of protection. In addition to strong T cell immunity, IV BCG vaccination was associated with a robust expansion of humoral immune responses that tracked with bacterial control. However, given the near complete protection afforded by high-dose IV BCG immunization, a precise correlate of immune protection was difficult to define. Here we leveraged plasma and bronchoalveolar lavage fluid (BAL) from a cohort of rhesus macaques that received decreasing doses of IV BCG and aimed to define the correlates of immunity across macaques that experienced immune protection or breakthrough infection following Mtb challenge. We show an IV BCG dose-dependent induction of mycobacterial-specific humoral immune responses, both in the plasma and in the airways. Moreover, antibody responses at peak immunogenicity significantly predicted bacterial control following challenge. Multivariate analyses revealed antibody-mediated complement and NK cell activating humoral networks as key functional signatures associated with protective immunity. Collectively, this work extends our understanding of humoral biomarkers and potential mechanisms of IV BCG mediated protection against Mtb .
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.07.31.551245
- https://www.biorxiv.org/content/biorxiv/early/2023/08/02/2023.07.31.551245.full.pdf
- OA Status
- green
- Cited By
- 7
- References
- 18
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385488345
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4385488345Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.07.31.551245Digital Object Identifier
- Title
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Humoral correlates of protection againstMycobacterium tuberculosisfollowing intravenous Bacille Calmette-Guérin vaccination in rhesus macaquesWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-08-02Full publication date if available
- Authors
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Edward B. Irvine, Patricia A. Darrah, Shu Wang, Chuangqi Wang, Ryan P. McNamara, Mario Roederer, Robert A. Seder, Douglas A. Lauffenburger, JoAnne L. Flynn, Sarah M. Fortune, Galit AlterList of authors in order
- Landing page
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https://doi.org/10.1101/2023.07.31.551245Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/08/02/2023.07.31.551245.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2023/08/02/2023.07.31.551245.full.pdfDirect OA link when available
- Concepts
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Immunology, Vaccination, Humoral immunity, Immune system, Mycobacterium tuberculosis, Immunization, Antibody, Immunity, Tuberculosis, Medicine, Immunogenicity, Virology, PathologyTop concepts (fields/topics) attached by OpenAlex
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7Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 4, 2023: 1Per-year citation counts (last 5 years)
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18Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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